Interleukin 2 inhibitor is a substance having interleukin 2 inhibitory activity. Known as examples of such substance are interleukin 2 production inhibitory substance and interleukin 2 signal transduction inhibitory substance. Interleukin 2 is necessary for activating T cells to proliferate. Interleukin 2 inhibitor shows an immunosuppressive effect through the T cell activating mechanism.
In recent years, interleukin 2 inhibitors have been tried for the treatment of various inflammations or diseases accompanying inflammations. For example, macrolide compounds such as FK506 and cyclosporins are known to be effective for the treatment of allergic conjunctivitis, allergic dermatitis and allergic rhinitis (U.S. Pat. Nos. 5,514,686, 5,385,907, etc.). Prior to this, the present inventor has reported that interleukin 2 inhibitor(s) comprising macrolide compound(s) such as FK506 are effective for the treatment of dry eye (WO00/66122) and topical ophthalmic treatment of ocular inflammations (U.S. Provisional Application No. 60/283,169, now PCT/JP02/03664).
However, in the topical treatment of various inflammations using interleukin 2 inhibitor, the immunosuppressive effect caused by interleukin 2 inhibitor may result in such side effects as infections. Accordingly, it is desired to develop anti-inflammatory agents reducing such side effects without adversely affecting main effects of interleukin 2 inhibitor.
Meanwhile, antimicrobial agents have been used for the ocular or dermal infection and the prevention of postoperative infection. In treating such infections, it is very important to prevent the proliferation and spread of microorganism at pathologically changed locations. Likewise, it is very important to inhibit the accompanying inflammations or an excessive immuno-inflammatory reaction following phylaxis. In order to meet such requirements, steroid drugs are mainly used as additional anti-inflammatory agents. However, using steroid drugs has the risk of causing such side effects as accentuation of infections by microorganism at pathologically changed locations; thinning of skin and pilosebaceous abnormal activation; weakened vascular wall in the air duct or nasal cavity; and steroidal glaucoma in the eye. Therefore, it is desired to develop safe and effective antimicrobial agent for the treatment of infections and their accompanying inflammations or infections showing an excessive immuno-inflammatory reaction following phylaxis.